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May 28, 2021/Bio Valley BIOON/---Ordinary mice cannot be infected with HIV, and previous HIV mouse models used mice carrying human stem cells or CD4 T cells, of which human CD4 T cells are a type of Immune cells that can infect HIV
.
But these models are often of limited utility, because human cells will quickly see the mouse host’s tissues as "foreign" and attack them, causing the mice to become seriously ill
In a new study, American researchers have developed a unique preclinical mouse model
.
In order to prevent mouse tissues from being attacked, a subset of human CD4 T cells carried by this model basically excludes cells that would attack mouse tissues
These authors anticipate that this will become a valuable and widely used tool to study the basic science of HIV infection and accelerate the development of better therapies
.
This new mouse model is part of an extensive effort to develop and test cell therapies against HIV infection
These authors found in this study that the problem of cell attacking the host previously found in mouse models is mainly caused by so-called "naïve" CD4 cells
.
These are human CD4 cells that have not yet come into contact with the target, and apparently include a cell population capable of attacking multiple mouse proteins
These authors observed that these human memory CD4 cells can also be infected and killed by HIV, and can also be protected by standard anti-HIV drugs, basically in the same way as in humans
.
Therefore, they discovered that these mice--what they call participant-derived xenograft (PDX) mice--can be used as a viable model for studying long-term HIV infection
Finally, the authors used this new mouse model to study a prospective new T cell-based therapy that is very similar to the CAR-T cell therapy for cancer that is now being tested
.
They implanted memory CD4 T cells from human donors into mice to allow HIV infection, and then after the infection was established, they injected another type of human T cells (CD8 T cells, also called killer T cells) into the mice.
These killer T cells and memory CD4 T cells come from the same human donor and can recognize the fragile structures on HIV, so they will attack the virus when they find the virus in mice
.
In order to improve the effectiveness of killer T cells, these authors stimulated them with a T cell stimulating protein called IL-15
This treatment method effectively suppressed HIV in mice
.
Although, as often seen in human cases, this virus has evolved to eventually evade the recognition of killer T cells, the ease of use of this mouse model allows these authors to monitor and study these long-term infections and viruses in detail.
Reference materials:
Reference materials:Chase D.
McCann et al.
A participant-derived xenograft model of HIV enables long-term evaluation of autologous immunotherapies.
Journal of Experimental Medicine, 2021, doi:10.
1084/jem.
20201908.
